1. Field of the Invention
The present invention relates to a method for allowing titanium-binding ferritin, the surface of which being modified with a peptide that recognizes and binds to titanium, to be selectively aligned on titanium on a substrate surface. Furthermore, the present invention relates to a method for regularly arranging inorganic particles which had been included in titanium-binding ferritin on titanium formed on a substrate.
2. Related Art
Particles (inorganic particles) which include a protein and an inorganic substance and which are arranged on a substrate have attracted attention in industrial fields of catalysts, sensors, biochips, transistors, semiconductors lasers, magnetic discs, displays and the like. In particular, patterning techniques have been desired in which inorganic particles are selectively arranged in a specified region, or they are regularly arranged in a fine region of nano-size, when the inorganic particles are industrially applied. Furthermore, in recent years, aiming at miaturization of total analysis systems including biosensors, applications to fine chemical substance analysis systems (Micro Total Analysis System (μTAS)) have also attracted attention. Behind such a situation, advantages such as improvement of biocompatibility, enablement of lowering of the cost due to mass productivity and measurement in the place (being portable) and the like are involved.
Techniques for selectively arranging proteins or inorganic particles on a solid surface involve extraordinary difficulty because it is very difficult to allow the surface of the protein and the inorganic substance to have a self-recognizing function. Known methods for forming a fine pattern using a protein that is a biomolecule include a method in which photolithography is utilized (see, A. S. Blawas, W. M. Reichert, Biomaterials, 19, 595 (1998)), microcontact printing (see, A. Bernard, J. P. Renault, B. Michel, H. R. Bosshard, E. Delamarche, Adv. Mater., 12, 1067 (2000)), dip-pen nanolithography (see, K. B. Lee, S. J. Park, C. A. Mirkin, J. C. Smith, M. Mrksick, Science, 295, 1702 (2002)), and the like. However, in light of mass productivity and costs, techniques for carrying out patterning of fine particles in a nano-size region have been demanded. Furthermore, a method for regularly arranging nano-size particles surrounded by a protein molecule is disclosed in Japanese Patent Provisional Publication No. H11-204774.
In these methods, procedures of: subjecting the surface of a SAM membrane (self-assembled monomolecular membrane), an LB membrane (monomolecule accumulating membrane) or the like to a processing for selectively arranging the particles; executing patterning of the particles through further conducting photolithography in combination; forming a region in which the inorganic particles are selectively arranged on a substrate by direct drawing or the like of a pattern on the substrate with a nanoprobe such as AFM (Atomic Force Microscope) or the like; and thereafter arranging the inorganic particles.
Hereinafter, a method for arranging inorganic particles using an LB membrane (PBLH membrane) according to the conventional method (Japanese Patent Provisional Publication No. H11-204774) will be illustrated with reference to FIGS. 1A to 1H.
First, in the step shown in FIG. 1A, a buffer 11 is reserved in a water bath 10 made of Teflon™, and naturally occurring ferritin 21 including an inorganic particle 20 therein is dispersed in this buffer.
Next, in the step shown in FIG. 1B, a PBLH membrane 30 is overlaid on the liquid surface of the solution. Then, the pH is adjusted with an appropriate acid alkaline solution. Because ferritin is negatively charged contrary to the PBLH membrane surface being positively charged, the naturally occurring ferritin 21 is attached on the PBLH membrane.
Next, in the step shown in FIG. 1C, a substrate (silicon substrate) 40 which had been subjected to a hydrophobic surface treatment is floated on the liquid surface on which the PBLH membrane was overlaid, thereby allowing the PBLH membrane on which the naturally occurring ferritin is attached to be adhered on the substrate.
Next, in the step shown in FIG. 1D, the silicon substrate 40 having the adhered PBLH membrane on which the naturally occurring ferritin is attached is removed from the water bath.
Next, in the step shown in FIG. 1E, after covering the surface of the face on which the naturally occurring ferritin is attached with a buffer solution 11, ultraviolet irradiation is performed using an adequate mask pattern 50. The naturally occurring ferritin in the region on which ultraviolet ray was irradiated is decomposed, and dispersed in the solution.
Next, in the step shown in FIG. 1F, the silicon substrate 40 after executing the patterning shown in FIG. 1E is washed with water.
Next, in the step shown in FIG. 1G, the silicon substrate 40 is dried to obtain the pattern arrangement of the naturally occurring ferritin including the inorganic particle therein.
Thereafter, in the step shown in FIG. 1H, a heat treatment at 500° C. is carried out in an inert gas 60 (for example, in nitrogen) to bake to burn out the naturally occurring ferritin including the inorganic particle therein and the PBLH membrane, thereby providing secondary pattern arrangement of the inorganic particles on the substrate. This structure is further processed to give a structure required for the device as described above.
However, according to the aforementioned conventional method, the SAM membrane is formed on the substrate side, and patterning is executed on the SAM membrane using an ultraviolet ray, or an LB membrane that is an adsorption membrane of the inorganic particle is utilized as the intermediate layer with respect to the substrate. Therefore, there are possibilities that the steps may be complicated, or that impurities included in the constituents of the SAM membrane or the LB membrane, or in the solution remain on the arranged surface of the inorganic particles whereby causing adverse influences on the device. Accordingly, an object of the present invention is to provide a technique for selectively and regularly arranging inorganic particles, in particular, those having a diameter of several to several ten nanometers in a necessary region and in a necessary amount with high mass productivity at low costs, without need of an intermediate layer, by allowing the inorganic particle side to have a recognizing ability of the base material on a substrate.